We were in discussion this morning and the question of affinities came
up. There seems to be a long(ish) standing issue about the repertoire
that goes something like...
Simplicus: The repertoire is made up of memory cells with very high
specificity (=fast on rate slow off rate) Abs plus the pool of newly
generated Ab rearrangements that are made throughout ontology.
Complexicus: No it is made of up of many lower affinity Abs with
"overlapping" specificities. Specificity comes from this overlap. I
don't want to talk about memory cells right now I am trying to imagine
how what I just suggested might work...
Now I find it very reasonable that our intuitions are a bit skewed by
our use of Abs as reagents. We select for Abs that will bring
proteins down in an immunoprecipitation. Surely this isn't the
bottomeline for a working immune system. Rather we have issues of
residence time, how long do we have to associate Ab with Fc receptor to
pull in another cascade of effector functions.
We also have the data from Zoller (Scand J Immunol 31, 619-629 1990)
and Coutinho (Dighiero, Lymberi, Holmberg, Lundquist, Coutinho &
Avrameas J. Immunol 134 p765 1984) that neonate B cells are of wider
specificity. How are we to interpret these things? It seems to me
that until we have a good sense of the dynamics of repertoire to a
successful passage through an infection this will cause unnecessary
argument. Do any of you have sources for papers addressing these
issues?
Thank you,
Jeremy Creighton Ahouse
Biology and Center for Complex Systems
Brandeis University
Waltham, MA 02254-9110